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This paper presents lifetime and 12-month prevalence rates and comorbidity data for substance abuse disorders among homeless and runaway adolescents. Data are from baseline interviews of a longitudinal diagnostic study of 428 (187 males and 241 females) homeless and runaway adolescents aged 16 to 19 years (mean age = 17.4 years, SD = 1.05). The data were collected by full-time interviewers on the streets and in shelters in eight Midwestern cities of various populations. About two thirds (60.5%) of the runaways met lifetime criteria for at least one of three substance disorders (alcohol abuse, alcohol dependence, drug abuse), and nearly one half (48.1%) met 12-month criteria for at least one of the disorders. Nearly all of the adolescents (93%) who met criteria for a substance disorder met criteria for at least one other mental disorder. Those factors most predictive of meeting lifetime criteria include parenting practices, experience of abuse, and association with deviant peers.